This study continues a long term investigation of the mechanisms which may control the transcription and translation of histone mRNA during the HeLa S-3 cell cycle. In the initial stages of this project we hope to use in vitro protein synthesis and DNA-RNA hybridization assays to determine if transcriptional control of histone mRNA function exists in HeLa cells and inhibits the synthesis of histone mRNA in G1 of the cell cycle. If such a mechanism can be demonstrated to exist in vivo we hope to be able to isolate the control factor or factors responsible for the initiation of histone mRNA production as cells proceed from G1 into S phase of the mitotic cycle. In later stages of the proposed investigations, we hope to be able to elucidate: a. The mechanisms controlling histone mRNA translation in the HeLa cell cycle; b. The location of histone genes on human and other chromosomes; c. The time of histone gene replication during the HeLa cell cycle; d. The means by which histone synthesis is coupled with DNA replication in HeLa cells; e. The mechanism by which histone polypeptide modifications are intrained with other cell cycle events. BIBLIOGRAPHIC REFERENCES: Stephens, R.E., C-J. Pan, K. Ajiro, T. Dolby and T. Borun. Studies of human histone messenger RNA. I. Methods for the isolation and partial characterization of RNA fractions containing human histone message from HeLa S-3 polyribosomes. J. Biol. Chem. Dec./Jan. 1976/77, in press. Borun, T.W., K. Ajiro, A. Zweidler, T.W. Dolby and R.E. Stephens. Studies of human histone messenger RNA. II. The resolution of fractions containing individual human histone messenger RNA species. J. Biol. Chem. Dec./Jan. 1976/77, in press.